Chiral Molecules with Two Chirality Centers

When a molecule contains two chirality centers, as does 2,3-dihydroxybutanoic acid, how many stereoisomers are possible  

We can use straightforward reasoning to come up with the answer. The absolute configuration at C-2 may be or 5. Likewise, C-3 may have either the / or the 5 configuration. The four possible combinations of these two chirality centers are 

Stereoisomer I is not a mirror image of III or IV, so it is not an enantiomer of either one. Stereoisomers that are not related as an object and its mirror image are called diaster-eomers diastereomers are stereoisomers that are not mirror images. Thus, stereoisomer I is a diastereomer of HI and a diastereomer of IV. Similarly, H is a diastereomer of III and IV. 

To convert a molecule with two chirality centers to its enantiomer, the configuration at both centers must be changed. Reversing the configuration at only one chirality center converts it to a diastereomer. 

Stereoisomeric 2,3-dihydroxybutanoic acids. Stereoisomers i and ii are enantiomers. Stereoisomers iii and iV are enantiomers. Aii other reiationships are diastereomeric (see text). 

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We have now seen many examples of compounds containing one tetrahedral stereogenic center. The situation is more complex for compounds with two stereogenic centers, because more stereoisomers are possible. Moreover, a molecule with two stereogenic centers may or may not be chiral. 

Merrifield method See solid phase peptide synthesis Meso stereoisomer (Section 7 11) An achiral molecule that has chirality centers The most common kind of meso com pound IS a molecule with two chirality centers and a plane of symmetry... 

In writing Eischer projections of molecules with two chirality centers, the molecule is arranged in an eclipsed conformation for projection onto the page, as shown in Eigure 7.9. Again, horizontal lines in the projection represent bonds coming toward you vertical bonds point away. 

Once we grasp the idea of stereoisomerism in molecules with two or more chirality centers, we can explore further details of addition reactions of alkenes. 

The maximum number of stereoisomers is 2" where n is the number of nonidentical chiral centers. Figure 1-2 shows the four stereoisomers present in a molecule with two chiral centers. Non-superimposable mirror images are enantiomers, while the other species in the figure are diastereomers. Unlike enantiomers, diastereomers have different physical properties. 

Diastereoisomers. Whereas compounds with one chiral center exist as an enantiomorphic pair, molecules with two or more chiral centers also exist as diastereoisomers (diastereomers). These are pairs of isomers with an opposite configuration at one or more of the chiral centers, but which are not complete mirror images of each other. An example is L-threonine which has the 2S, 3R configuration. The diastereoisomer with the 2S, 3S configuration is known as i-a//o-threonine. L-isoleucine, whose side chain is -CH(CH3) CH2CH3, has the 2S, 3R configuration. It can be called 2(S)-amino-3(R)-methyl-valeric acid but the simpler name L-isoleucine implies the correct configuration at both chiral centers. 

The basic principles of the mechanism of this Lewis-base-catalyzed aldol reaction have already been described in Section 6.2.1.1. With regard to the course of the enantio- and diastereoselective formation of aldol adducts with two stereogenic centers, it is proposed that synthesis of anti-products proceeds via a chair-like transition structure. A distinctive feature of the cationic transition state complex is a hexacoordinated silicon atom bearing two chiral phosphoramide molecules as ligands (Scheme 6.30). 

C Diastereomers of Molecules with Two or More Chirality Centers... 

A molecule with two chirality centers can have four possible stereoisomers. 

Biocatalysis is often used to prepare molecules with two or more chiral centers or to prepare intermediates from simple precursors when selective chemical transformations would be difficult [55]. Molecules with one chiral center are generally prepared by classical chemical resolution or by transferring chirality into achiral starting materials using chiral reagents. The launch of atorvastatin was initially carried out by classical conversion of 39 to the chiral diol 40 (Figure 3.27), and a biocatalyzed preparation of 40 was also developed [56]. The biocatalyzed route may now be the preferred route for preparing 40 [55]. 

Use of the chiral iron catalyst 28 for asymmetric sulfide oxidation was recently reported by Fontecave [48]. The complex is a dimer with two iron centers which are connected via a r -oxo bridge. Two bidentate (-)-4,5-pinene-bipyridine hg-ands 29 and one molecule of water are coordinated to each iron atom thus completing the octahedral environment of this diferric complex. Complex 28 can be isolated as a green solid with four perchlorates as counterions. 

It was indicated earlier that use of binary symbols to describe asymmetric centers in molecules is not always as simple as it might appear. In compounds with several asymmetric centers, the situation to be described becomes more complex. With two asymmetric centers, there are four possible configurations. Using the descriptors developed for carbon chemistry, the four isomers are RR, SS, RS, and SR. For three chiral centers we can have 23 or 8 isomers, RRR, SSS, SRS, RSR, RSS,... 

Dimethylmaleate hydratase (E.C. 4.2.1.85) has been described as the enzyme that catalyzes the addition of water to dimethylmaleate (11) to yield a molecule with two chiral centers, (2R,3S)-2,3-dimethylmalate (12)[I31. 

A molecule with two centers of chirality has the descriptor p (positive) if the centers carry the same (R.S)-descriptor it has the descriptor n (negative) if the (R.S)-descriptors differ. 

Mefloquine 274 is a useful alternative treatment agent for Plasmodium vivax malaria and Plasmodium falciparum malaria in areas, where chloroquine is still recommended as the first-hne therapeutic agent.Mefloquine is a chiral molecule with two asymmetric carbon centers, and it exists as a mixture of diastereomers. The drug is currently manufactured and sold as a racemate of the (+1—) R,S enantiomers by Hoffman-LaRoche. The (+) enantiomer is more effective in treating malaria, and the (—) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects.It is not known whether mefloquine can be transformed into its stereoisomer in vivo. 

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